Integrating Geriatric Assessment and Genetic Profiling to Personalize Therapy Selection in Older Adults with Acute Myeloid Leukemia (AML)

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.120-120
• Main Authors: Bhatt, Vijaya R., Wichman, Christopher, Al-Kadhimi, Zaid S., Koll, Thuy T., Berger, Ann, Armitage, James O., Holstein, Sarah A., Gundabolu, Krishna, Maness, Lori J.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-124375

Introduction: Geriatric assessment can predict the risk of toxicities of chemotherapy in older adults. Genetic risk categories correlate with survival following intensive chemotherapy in AML. Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative precision medicine approach to personalize therapy selection in older adults with AML. We report results of a pre-planned interim analysis of a pragmatic phase II trial using such strategy that has an overarching goal to reduce early mortality (NCT03226418). Methods: Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for intensive chemotherapy (Table 1). Additional assessment included Karnofsky Performance Scale (KPS), Patient Health Questionnaire-9 (PHQ-9), and Mini Nutritional Assessment-Short Form (MNA). Genetic profiling for therapy selection relied on karyotyping and followed the 2017 European LeukemiaNet criteria. While available mutation test results were incorporated to risk stratify, the study did not require to wait for the results prior to therapy initiation given an anticipated turnaround time of 1-2 weeks for mutation test results. Therapy selection followed the algorithm demonstrated in Figure 1. Patients with good or intermediate-risk AML received intensive chemotherapy such as 7+3 +/- gemtuzumab or midostaurin if determined to be fit. Patients with high-risk AML received low-intensity chemotherapy such as a hypomethylating agent with or without novel drugs, or CPX 351 if they were fit and met the FDA-approved indications. Patients with organ dysfunction (e.g. creatinine ≥2 mg/dl) and those requiring chemotherapy for other malignancy received low-intensity chemotherapy. Chemotherapy at diagnosis or follow up could be administered in community oncology settings. Patients were followed for assessment of quality of life, functional and oncologic outcomes. Results: Between July 2017-June 2019, a total of 31 patients (including 1 MDS patient considered screen failure) were enrolled. The pre-planned interim analysis results are based on the first 27 AML patients. Baseline characteristics included a median age of 70 years (range 60-84 years), 56% female, 96% white, and a median KPS of 80% (range 60-100%). As presented in Table 1, over half of the patients had ≥3 comorb